Controlling Fever-Induced Seizures

Main Category: Infectious Diseases / Bacteria / Viruses
Also Included In: Pediatrics / Children's Health;  Neurology / Neuroscience;  Genetics
Article Date: 24 Aug 2007 - 8:00 PST

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When your body cranks up the heat, it's a sign that something's wrong -- and a fever is designed to help fight off the infection. But turning up the temperature can have a down side: in about one in 25 infants or small children, high fever can trigger fever-induced (febrile) seizures. While the seizures themselves are generally harmless, a prolonged fever resulting from infection or heatstroke of over 108˚F (42˚C) can eventually lead to respiratory distress, cognitive dysfunction, brain damage or death.

New research by scientists at the University of Toronto Mississauga and Queen's University has shown that genetic variation in the foraging gene results in different tolerance for heat stress, and demonstrates how the use of specific drugs can replicate this effect in fruit flies and locusts. While the findings are at an early stage, the researchers suggest that since this genetic pathway is found in other organisms, it could lead to ways to rapidly protect the brain from extremely high fevers in mammals, including humans. The new study appears in the journal PLoS ONE, the online, open-access journal from the Public Library of Science.

"Our research suggests that manipulation of a single gene or genetic pathway will be sufficient to rapidly protect the nervous system from damage due to extreme heat stress," says senior researcher, Professor Marla B. Sokolowski, who holds a Canada Research Chair in Genetics.

In their research, post-doctoral fellow Ken Dawson-Scully and Sokolowski demonstrate that the foraging gene, responsible for a protein called PKG, protects against heat-induced neural failure in fruit flies and locusts. When they increased the temperature by 5˚C per minute (starting from 22˚C and rising to 42˚C), they found that fruit flies with a lower level of PKG experienced neural failure at much higher temperatures than those with higher levels of PKG.

Using drugs that interact with the PKG molecule, the researchers showed it is possible to induce an extremely rapid protection of neural function during heat stress. Queen's biologists Gary Armstrong and Mel Robertson exposed locusts to increasing heat while monitoring the neural circuit that controls breathing. At approximately 30˚C (about three minutes before expected neural failure), the researchers injected the locusts with a PKG inhibitor. Compared to locusts who received a placebo injection, the treated locusts showed a rapid and significant protection of their neural circuitry.

"During heat trauma to the brain, there exists a window of opportunity between the time of occurrence of neural dysfunction and eventual brain damage or death," says Dawson-Scully. "Manipulation of the PKG pathway during this period should increase an individual's chance of survival."

The research was supported by the Heart and Stroke Foundation of Canada, the Canadian Institutes of Health Research and the Natural Sciences and Engineering Research Council of Canada.

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Article adapted by Medical News Today from original press release.
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The following press release refers to an upcoming article in PLoS ONE. The release has been provided by the article authors and/or their institutions. Any opinions expressed in this are the personal views of the contributors, and do not necessarily represent the views or policies of PLoS. PLoS expressly disclaims any and all warranties and liability in connection with the information found in the release and article and your use of such information.

Contact:
Marla Sokolowski University of Toronto Mississauga
Ken Dawson-Scully University of Toronto Mississauga

Citation: Dawson-Scully K, Armstrong GAB, Kent C, Robertson RM, Sokolowski MB (2007) Natural Variation in the Thermotolerance of Neural Function and Behavior due to a cGMP-Dependent Protein Kinase. PLoS ONE 2(8): e773. doi:10.1371/journal.pone.0000773

http://www.plosone.org/doi/pone.0000773

Source: Nicolle Wahl
Public Library of Science